Ancestral haplotype (AH) 8.1(HLA-A1, Cw7, B8, TNFAB*a2b3, TNFN*S, C2*C, Bf*s, C4A*Q0, C4B*1, DRB1*0301, DRB3*0101, DQA1*0501, DQB1*0201) seems to be associated with susceptibility to autoimmune ...diseases. Different mechanisms are probably involved in increasing autoimmunity, such as unbalanced cytokine production and the lack of C4A protein. So AH 8.1 modifies immune response in many ways. In this study we demonstrate that IgG2 serum levels were significantly lower in 8.1 AH carriers than in 8.1 AH non-carriers. On the contrary, as regards IgG1, IgG3, IgG4 serum levels, no significant differences were observed between the two groups. In AH 8.1 carriers low IgG2 levels might take to slower clearance of the infectious agent and hence to a lasting presence of it. The persistence of infectious antigens could determine an increased production of autoantibodies with a higher risk of cross-reactions.
to evaluate the association between baseline and lifetime alcohol consumption and the risk of epithelial cancer (all types) in the Italian cohort of the European Prospective Investigation into Cancer ...and nutrition (EPIC) study.
prospective study carried out in a large Italian population.
detailed information on the consumption of alcoholic beverages at baseline and over lifetime collected at enrolment into the EPIC study (1993-1998) by standardised questionnaires for 44,477 healthy adults.
2,640 incident epithelial cancers identified during a mean follow-up of 11.4 years. Multivariate Cox proportional hazard models adjusted for several potential confounders were used to calculate hazard ratios (HR) and corresponding 95% confidence intervals (CI).
lifetime alcohol consumption (p for trend =0.005) was associated with epithelial cancer risk in the whole cohort. This effect was more evident in women (p =0.049) and in current smokers (p =0.012). Alcohol consumption at baseline was associated with the epithelial cancer risk in women (p for trend =0.01) and current smokers (p for trend =0.02). A significant interaction between alcohol consumption and smoke duration (p =0.015 for baseline; p =0.006 for lifetime) was identified.
in this large Italian population, alcohol consumption, particularly lifetime, is a significant risk factor for the development of epithelial cancers. This effect appears to be modulated by smoking habits.
Summary Background Epidemiologic studies have demonstrated that elderly patients with fixed airflow obstruction can be affected by asthma or chronic obstructive pulmonary disease (COPD). Methods We ...studied 49 consecutive elderly outpatients, presenting fixed airflow obstruction, by clinical history (smoking), pulmonary function tests, blood gas analysis, and induced sputum. Results The age was not different in patients with COPD ( n =28) and asthma ( n =21) (70.2±3.9 years vs. 69.6±3.7 years), also the degree of fixed airflow obstruction was similar (FEV1 : 58.3±1.5% vs. 59.0±1.4% of predicted). Patients with asthma had significantly more eosinophils in peripheral blood (0.43±0.05×10−3 μL vs. 0.27±0.1×10−3 μL, P <0.0001), and in induced sputum (5.0% (p25th and p75th) 5.0–6.0% vs. 1.0% (p25th and p75th) 0.01–1.0%; P <0.0001), as well as serum ECP (18.6±4.9 ng/mL vs. 7.7±4.7 ng/mL, P <0.0001) and ECP in the induced sputum (31.6±2.9 ng/mL vs. 5.6±4.9 ng/mL, P <0.0001). Finally, in induced sputum the eosinophils EG2+ were higher in patients with asthma than in patients with COPD (40.5 (p25th and p75th) 39.3–44.3 MFI vs. 3.9 (p25th and p75th) 0–11.4 MFI, P <0.0001). They also had significantly higher diffusing capacity, and a greater reversibility to steroids, after 14-day course of therapy, whereas the reversibility to 400 μg of salbutamol was similar. Conclusion Despite similar fixed airflow obstruction, elderly patients with asthma have distinct characteristics compared with patients with COPD.
Background: Several experimental studies have suggested potential anticarcinogenic effects of flavonoids, although epidemiologic evidence for the impact of dietary flavonoids on risk of gastric ...cancer (GC) is limited.Objective: We investigated the association between intake of dietary flavonoids and lignans and incident GC.Design: The study followed 477,312 subjects (29.8% men) aged 35–70 y from 10 European countries who participated in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Validated dietary questionnaires and lifestyle information were collected at baseline. A food-composition database on flavonoids and lignans was compiled by using data from USDA and Phenol-Explorer databases.Results: During an average follow-up of 11 y, 683 incident GC cases (57.8% men) were mostly validated by a panel of pathologists and used in this analysis. We observed a significant inverse association between total flavonoid intake and GC risk in women (HR: 0.81; 95% CI: 0.70, 0.94; for the continuous variable after log2 transformation) but not in men (HR: 0.97; 95% CI: 0.85, 1.09). In women, significant inverse associations with GC risk were also observed for intakes of some flavonoid subgroups (anthocyanidins, flavonols, flavones, and flavanols), particularly with intestinal type tumors for total flavonoid and flavanol intakes (P-heterogeneity < 0.1). After stratification by smoking status and sex, there was no significant heterogeneity in these associations between ever- and never-smokers.Conclusion: Total dietary flavonoid intake is associated with a significant reduction in the risk of GC in women.
Expression of the human cytomegalovirus (HCMV)-encoded chemokine receptor homologue pUS28 in mammalian cells results in ligand-dependent and -independent changes in the activity of multiple cellular ...signal transduction pathways. The ligand-dependent signalling activity of pUS28 has been shown to be predominantly mediated by heterotrimeric G proteins of the G(i/o) and G(12/13) subfamilies. Ligand-independent constitutive activity of pUS28 causing stimulation of inositol phosphate formation has been correlated with the coupling of pUS28 to G proteins of the G(q) family. It is well known that activation of G(q) proteins by cell surface receptors is coupled to activation of the Rho GTPase RhoA. Activated RhoA regulates numerous cellular functions, including the activity of the transcription factor serum response factor (SRF). The marked activation of G(q) proteins by pUS28 in transfected and HCMV-infected cells prompted us to investigate its effect on SRF activity. The results presented herein demonstrate that expression of pUS28 in COS-7 cells caused a vigorous induction of SRF activity. This effect was observed in the absence of chemokines known to interact with pUS28, and was specifically mediated by endogenous G(q) and/or G(11) as well as RhoA and/or a closely related Rho GTPase. The stimulatory effect of pUS28 and Galpha(q/11) was independent of phospholipase C-beta (PLCbeta) activation and was markedly sensitive to inhibition by wild-type, but not by constitutively active Galpha(16), thus identifying Galpha(16) as a modulator of Galpha(q/11) function likely to act by competing with Galpha(q/11) for and thus uncoupling Galpha(q/11) from activation by pUS28.
Expression of the human cytomegalovirus (HCMV)-encoded chemokine receptor homologue pUS28 in mammalian cells results in ligand-dependent and - independent changes in the activity of multiple cellular ...signal transduction pathways. The ligand-dependent signalling activity of pUS28 has been shown to be predominantly mediated by heterotrimeric G proteins of the G sub(i/o) and G sub(12/13) subfamilies. Ligand-independent constitutive activity of pUS28 causing stimulation of inositol phosphate formation has been correlated with the coupling of pUS28 to G proteins of the G sub(q) family. It is well known that activation of G sub(q) proteins by cell surface receptors is coupled to activation of the Rho GTPase RhoA. Activated RhoA regulates numerous cellular functions, including the activity of the transcription factor serum response factor (SRF). The marked activation of G sub(q) proteins by pUS28 in transfected and HCMV-infected cells prompted us to investigate its effect on SRF activity. The results presented herein demonstrate that expression of pUS28 in COS-7 cells caused a vigorous induction of SRF activity. This effect was observed in the absence of chemokines known to interact with pUS28, and was specifically mediated by endogenous G sub(q) and/or G sub(11) as well as RhoA and/or a closely related Rho GTPase. The stimulatory effect of pUS28 and G alpha sub(q/11) was independent of phospholipase C- beta (PLC beta ) activation and was markedly sensitive to inhibition by wild-type, but not by constitutively active G alpha sub(16), thus identifying G alpha sub(16) as a modulator of G alpha sub(q/11) function likely to act by competing with G alpha sub(q/11) for and thus uncoupling G alpha sub(q/11) from activation by pUS28.
We have performed extended x-ray absorption fine-structure (EXAFS) spectroscopy on a 2.8% Cr-doped V2O3 sample, with the aim of studying its structural evolution in a wide temperature range across ...the paramagnetic-antiferromagnetic insulating phase transition at Tc. The data were registered with two different set-ups in fluorescence and transmission geometries, for polarized and unpolarized spectra, respectively. Our idea, based on previous experiments reported in the literature, is that extended structural modifications of the nominal trigonal symmetry are present in the paramagnetic insulating phase for several tens of degrees above Tc, involving further-nearest-neighbor vanadium ions. Our data confirm that the paramagnetic insulating phase is not structurally homogeneous in a temperature range of about 30 K around Tc, where local distortions of monoclinic symmetry involving further-nearest neighbors are present. Moreover, the analysis of the absorption profile at Cr K-edge suggests that Cr ions enter the lattice randomly. We finally analyze our findings in light of current theoretical models.
: Ancestral haplotype (AH) 8.1(HLA‐A1, Cw7, B8, TNFAB*a2b3, TNFN*S, C2*C, Bf*s, C4A*Q0, C4B*1, DRB1*0301, DRB3*0101, DQA1*0501, DQB1*0201) seems to be associated with susceptibility to autoimmune ...diseases. Different mechanisms are probably involved in increasing autoimmunity, such as unbalanced cytokine production and the lack of C4A protein. So AH 8.1 modifies immune response in many ways. In this study we demonstrate that IgG2 serum levels were significantly lower in 8.1 AH carriers than in 8.1 AH non‐carriers. On the contrary, as regards IgG1, IgG3, IgG4 serum levels, no significant differences were observed between the two groups. In AH 8.1 carriers low IgG2 levels might take to slower clearance of the infectious agent and hence to a lasting presence of it. The persistence of infectious antigens could determine an increased production of autoantibodies with a higher risk of cross‐reactions.
Thin‐film neural devices are an appealing alternative to traditional implants, although their chronic stability remains matter of investigation. In this study, a chronically stable class of thin‐film ...devices for electrocorticography is manufactured incorporating silicon carbide and diamond‐like carbon as adhesion promoters between glassy carbon (GC) electrodes and polyimide and between GC and platinum traces. The devices are aged in three solutions—phosphate‐buffered saline (PBS), 30 × 10−3 and 150 × 10−3m H2O2/PBS—and stressed using cyclic voltammetry (2500 cycles) and 20 million biphasic pulses. Electrochemical impedance spectroscopy (EIS) and image analysis are performed to detect eventual changes of the electrodes morphology. Results demonstrate that the devices are able to undergo chemically induced oxidative stress and electrical stimulation without failing but actually improving their electrical performance until a steady state is reached. Additionally, cell viability tests are carried out to verify the noncytotoxicity of the materials, before chronically implanting them into rat models. The behavior of the GC electrodes in vivo is monitored through EIS and sensorimotor evoked potential recordings which confirm that, with GC being activated, impedance lowers and quality of recorded signal improves. Histological analysis of the brain tissue is performed and shows no sign of severe immune reaction to the implant.
The incorporation of silicon carbide and diamond‐like carbon as adhesion promoters between glassy carbon (GC) electrodes and polyimide and between GC and platinum traces greatly improves in vitro and in vivo stability of GC electrocorticography (ECoG) arrays. The devices undergo chemically induced oxidative stress and electrical stimulation without delaminating and failing. After chronic implants, no sign of severe immune reaction is shown.
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